Dataset Information

Epitope analysis of the collagen type V-specific T cell response in lung transplantation reveals an HLA-DRB1*15 bias in both recipient and donor.

ABSTRACT:

Background

IL-17-dependent cellular immune responses to the ?1 chain of collagen type V are associated with development of bronchiolitis obliterans syndrome after lung transplantation, and with idiopathic pulmonary fibrosis and coronary artery disease, primary indications for lung or heart transplantation, respectively.

Methodology/principal findings

We found that 30% of the patients awaiting lung transplantation exhibited a strong cell-mediated immune response to col(V). Of these, 53% expressed HLA-DR15, compared to a 28% HLA-DR15 frequency in col(V) low-responders (p=0.02). After transplantation, patients with HLA-DR1 and -DR17, not -DR15, developed anti-col(V) responses most frequently (p=0.04 and 0.01 vs. controls, respectively). However, recipients of a lung from an HLA-DR15(+)donor were at significantly elevated risk of developing anti-col(V) responses (p=0.02) and BOS (p=0.03). To determine the molecular basis of this unusual pattern of DR allele bias, a peptide library comprising the collagenous region of the ?1(V) protein was screened for binding to HLA-DR0101, -DR1501, -DR0301 (DR17) or to HLA-DQ2 (DQA1*0501: DQB1*0201; in linkage disequilibrium with -DR17) and -DQ6 (DQA1*0102: DQB1*0602; linked to -DR15). Eight 15-mer peptides, six DR-binding and two DQ-binding, were identified. HLA-DR15 binding to two peptides yielded the highest binding scores: 650 (where 100 = positive control) for p799 (GIRGLKGTKGEKGED), and 193 for p1439 (LRGIPGPVGEQGLPG). These peptides, which also bound weakly to HLA-DR1, elicited responses in both HLA-DR1(+) and -DR15(+) col(V) reactive hosts, whereas binding and immunoreactivity of p1049 (KDGPPGLRGFPGDRG) was DR15-specific. Remarkably, a col(V)-reactive HLA-DR1(+)DR15(neg) lung transplant patient, whose donor was HLA-DR15(+), responded not only to p799 and p1439, but also to p1049.

Conclusions/significance

HLA-DR15 and IPF disease were independently associated with pre-transplant col(V) autoimmunity. The increased risk of de novo immunity to col(V) and BOS, associated with receiving a lung transplant from an HLA-DR15(+) donor, may result from presentation by donor-derived HLA- DR15, of novel self-peptides to recipient T cells.

SUBMITTER: Keller MR

PROVIDER: S-EPMC3827168 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Epitope analysis of the collagen type V-specific T cell response in lung transplantation reveals an HLA-DRB1*15 bias in both recipient and donor.

Keller Melissa R MR Haynes Lynn D LD Jankowska-Gan Ewa E Sullivan Jeremy A JA Agashe Vrushali V VV Burlingham Scott R SR Burlingham William J WJ

PloS one 20131112 11

<h4>Background</h4>IL-17-dependent cellular immune responses to the α1 chain of collagen type V are associated with development of bronchiolitis obliterans syndrome after lung transplantation, and with idiopathic pulmonary fibrosis and coronary artery disease, primary indications for lung or heart transplantation, respectively.<h4>Methodology/principal findings</h4>We found that 30% of the patients awaiting lung transplantation exhibited a strong cell-mediated immune response to col(V). Of these ...[more]

PMID: 24265781

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Dataset Information

Epitope analysis of the collagen type V-specific T cell response in lung transplantation reveals an HLA-DRB1*15 bias in both recipient and donor.

Background

Methodology/principal findings

Conclusions/significance

Publications

Epitope analysis of the collagen type V-specific T cell response in lung transplantation reveals an HLA-DRB1*15 bias in both recipient and donor.

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